Date: 2022-11-13 17:00 ~ 19:00
Speaker: Junseok Koh (SNU School of Biological Sciences)
Professor: 생명과학부
Location: 대면 | 목암홀(Mokam Hall) https://snu-ac-kr.zoom.us/j/94428091882
Molecular mechanisms of nucleocytoplasmic transport:
How intrinsically disordered proteins in the nuclear pore complex facilitate selective and fast
macromolecular transport
Abstract
Selective macromolecular trafficking between the nucleus and cytoplasm is mediated by the
nuclear pore complex (NPC) embedded in the nuclear envelope. The NPC is the largest
transport channel in the cell, assembled from 30 distinct protein subunits collectively termed
nucleoporins (Nups). Several Nups contain intrinsically disordered regions (IDRs) that lack
stable three-dimensional structures but instead interconvert among multiple conformational
states. These IDRs present multiple phenylalanine-glycine (FG) motifs that specifically bind
to transport factors (karyopherins, Kaps) carrying macromolecular cargos. Although these
interactions account for the transport selectivity, it remains elusive how such selective
interactions can simultaneously facilitate the fast (~ 1 ms) macromolecular transport through
the crowded central channel of the NPC. In this lecture, molecular mechanisms underlying
the fast transport will be derived from our recent structural and thermodynamic studies
demonstrating multivalent interactions of Nup IDRs with Kap. The suggested transport
mechanisms underscore the unique molecular features of IDRs that are distinct from ordered
proteins and consequently best suited for the dynamic transport process. Finally, our
paradigm on the IDR functions in nucleocytoplasmic transport will be expanded to other
biological systems, highlighting the extreme versatility of the intrinsic disorder ubiquitous in
the eukaryotic proteome.